Baricitinib improves clinical, functional, radiographic outcomes in RA
Early use of the oral Janus kinase 1/2 inhibitor baricitinib led to enhanced clinical, functional, and radiographic efficacy compared with methotrexate monotherapy in patients with rheumatoid arthritis (RA), according to data presented at EULAR 2019.
To assess the potential of early baricitinib therapy in achieving improved clinical and functional outcomes, researchers evaluated data from the RA-BEGIN* cohort (n=588, mean disease duration 1.4 years) wherein participants were randomized 4:3:4 to receive methotrexate once weekly, baricitinib 4 mg once daily (early-start group), or both for 52 weeks. A long-term extension phase ensued thereafter, whereby all participants were given baricitinib 4 mg. The methotrexate recipients who switched to baricitinib comprised the delayed-start group. [EULAR 2019, abstract THU0075]
Four weeks into the switch to baricitinib, the percentage of patients in the delayed-start arm who achieved low disease activity (SDAI** ≤11) and remission (SDAI ≤3.3) increased from 60 to 78 percent and 18 to 31 percent, respectively. At week 100, >80 percent of the population in both arms had low disease activity and nearly half achieved remission.
HAQ-DI*** scores were lower in the early- vs the delayed-start arm from baseline to week 52, diverging as early as week 1 (p≤0.001) up until week 52 (p≤0.01). The drop in HAQ-DI score in the delayed-start arm 4 weeks following the transition to baricitinib signified functional improvement, which was sustained up to week 100.
These findings underscore the potential of baricitinib in improving clinical and functional outcomes in methotrexate-naïve RA patients, noted the researchers. The transition from methotrexate to baricitinib led to favourable clinical improvements as early as 4 weeks post-switching. “However, if the goal of therapy is to achieve rapid and sustained control of disease activity, the differences [in] HAQ-DI [scores] … support earlier switch to baricitinib for patients who do not obtain disease control with methotrexate,” the researchers pointed out.
Haemoglobin in structural damage progression
In a post hoc analysis, researchers investigated the effect of baricitinib on structural damage progression based on baseline haemoglobin levels using data from RA-BEAM# (n=487, 328, and 488 for baricitinib 4 mg, adalimumab, and placebo, respectively) and RA-BEGIN. [EULAR 2019, abstract SAT0102]
Pooled results of both studies showed that participants with higher baseline haemoglobin levels were less likely to show structural damage progression at 52 weeks (adjusted odds ratio [adjOR], 0.76; p<0.001 [RA-BEAM] and adjOR, 0.72; p=0.001 [RA-BEGIN]), independent of other factors included in the multivariate regression model. This finding supports evidence reflecting an inverse association between haemoglobin levels and radiographic progression of structural joint damage in RA. [Arthritis Care Res (Hoboken) 2018;70:861-868; Ann Rheum Dis 2014;73:691-696]
In RA-BEAM, among patients with low or normal baseline haemoglobin levels, structural damage progression was less frequent in baricitinib or adalimumab vs placebo recipients (11.2 percent or 10.5 percent vs 32.6 percent [low haemoglobin level] and 7.6 percent or 6.5 percent vs 15.5 percent [normal haemoglobin level]).
In RA-BEGIN, patients with low baseline haemoglobin levels who received baricitinib alone/with methotrexate had lower rates of structural damage progression vs those on methotrexate monotherapy (18.3 percent/10.0 percent vs 35.6 percent). In patients with normal baseline haemoglobin, the difference between treatments was less pronounced (12.8 percent/10.1 percent vs 13.4 percent).
Taken together, the findings from both trials showed that baricitinib reduced structural damage progression, which was more pronounced in methotrexate-treated patients with low baseline haemoglobin levels, noted the researchers.
Further investigation is warranted to explore prognostic factors such as high-sensitivity C-reactive protein, disease duration, baseline erosion, and anti-citrullinated protein antibody positivity to aid clinicians in identifying suitable candidates for early baricitinib treatment, said the researchers.